Computer-aided prediction of biological activity spectra for organic compounds: the possibilities and limitations

Poroikov, Vladimir; Filimonov, Dmitry; Gloriozova, Tatyana A.; Lagunin, Alexey; Druzhilovskiy, Dmitry S.; Rudik, Anastasia V.; Stolbov, Leonid A.; Дмитриев, А. В.; Tarasova, O.; Ivanov, Sergey; Pogodin, Pavel V.

doi:10.1007/s11172-019-2683-0

Cited by 65 publications

(53 citation statements)

References 71 publications

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“…The profiles of potential pharmacological activity of compounds 2d‐f , 3a‐h, and 4a‐g were studied in silico using the PASS software. [ 44,45 ] For each activity, PASS calculates two probabilities, Pa and Pi. Pa and Pi values vary from 0.000 to 1.000, indicating the probabilities of the compound to be active or inactive, respectively.…”

Section: Resultsmentioning

confidence: 99%

Isoxazole derivatives of silatrane: synthesis, characterization, in silico ADME profile, prediction of potential pharmacological activity and evaluation of antimicrobial action

Адамович

Kondrashov

Ushakov

et al. 2020

Applied Organom Chemis

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A new family of mono‐ (3a‐h) and bis‐ (4a‐g) isoxazole‐bridged silatranes has been synthesized by the reaction of 3‐aminopropylsilatrane (1) and 3‐substituted 5‐chloro‐methylisoxazoles (2a‐h). The structure of the isoxazole‐silatrane hybrids is characterized by elemental analysis, FT‐IR, UV, NMR (1H, 13C,29Si and 15N) spectroscopy, high‐resolution mass spectrometry, and X‐ray diffraction analysis. The in silico ADME (absorption, distribution, metabolism, excretion) assessment reveals that properties of mono‐adducts (3a‐h) are similar to those of drugs obeyed to the Lipinski's rule. The calculated screening of potential pharmacological activity profiles (in silico PASS program) of isoxazole‐silatranes shows that all synthesized compounds (both mono‐ and bis‐substituted) may have high antitumor action, unlike starting isoxazoles. The preliminary screening of the synthesized silatranes for antimicrobial activity against Enterococcus durans, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa indicates that all test samples are active only against gram‐positive microorganisms. Silatrane 3f displays minimal inhibitory concentration (MIC 12.5 and 6.2 μg ml−1) against E. durans and B. subtilis as compared with standard drug gentamicin (MIC 25 and 50 μg ml−1).

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Section: Resultsmentioning

confidence: 99%

Isoxazole derivatives of silatrane: synthesis, characterization, in silico ADME profile, prediction of potential pharmacological activity and evaluation of antimicrobial action

Адамович

Kondrashov

Ushakov

et al. 2020

Applied Organom Chemis

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“…NSC765599 and NSC765690 were screened for potential drug target using SwissTarget prediction algorithm, which predicts potential drug target based on the principle of similarity [ 43 ]. In addition, we also employ the computer-aided Prediction of Biological Activity Spectra (PASS) web resources to predict the potential drug targets [ 44 ]. The activity patterns (fingerprints) of both NSC765599 and NSC765690 were correlated to NCI synthetic compounds, standard agents and molecular targets using the DTP-COMPARE algorithms [ 45 ].…”

Section: Methodsmentioning

confidence: 99%

Pharmacoinformatics and Preclinical Studies of NSC765690 and NSC765599, Potential STAT3/CDK2/4/6 Inhibitors with Antitumor Activities against NCI60 Human Tumor Cell Lines

et al. 2021

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Signal transducer and activator of transcription 3 (STAT3) is a transcriptional regulator of a number of biological processes including cell differentiation, proliferation, survival, and angiogenesis, while cyclin-dependent kinases (CDKs) are a critical regulator of cell cycle progression. These proteins appear to play central roles in angiogenesis and cell survival and are widely implicated in tumor progression. In this study, we used the well-characterized US National Cancer Institute 60 (NCI60) human tumor cell lines to screen the in vitro anti-cancer activities of our novel small molecule derivatives (NSC765690 and NSC765599) of salicylanilide. Furthermore, we used the DTP-COMPARE algorithm and in silico drug target prediction to identify the potential molecular targets, and finally, we used molecular docking to assess the interaction between the compounds and prominent potential targets. We found that NSC765690 and NSC765599 exhibited an anti-proliferative effect against the 60 panels of NCI human cancer cell lines, and dose-dependent cytotoxic preference for NSCLC, melanoma, renal, and breast cancer cell lines. Protein–ligand interactions studies revealed that NSC765690 and NSC765599 were favored ligands for STAT3/CDK2/4/6. Moreover, cyclization of the salicylanilide core scaffold of NSC765690 mediated its higher anti-cancer activities and had greater potential to interact with STAT3/CDK2/4/6 than did NSC765599 with an open-ring structure. NSC765690 and NSC765599 met the required safety and criteria of a good drug candidate, and are thus worthy of further in-vitro and in-vivo investigations in tumor-bearing mice to assess their full therapeutic efficacy.

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“…In this review, we will look at rare and unusual polycyclic endoperoxides isolated from different terrestrial and marine sources. The biological activity of many polycyclic endoperoxides has not been determined, and we present the pharmacological activities detected experimentally and predicted based on the structure-activity relationships using the PASS (Prediction of Activity Spectra for Substances) software [ 31 , 32 , 33 ]. PASS estimates the probabilities of several thousand biological activities with an average accuracy of about 96%.…”

Section: Introductionmentioning

confidence: 99%

Antiprotozoal and Antitumor Activity of Natural Polycyclic Endoperoxides: Origin, Structures and Biological Activity

et al. 2021

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Polycyclic endoperoxides are rare natural metabolites found and isolated in plants, fungi, and marine invertebrates. The purpose of this review is a comparative analysis of the pharmacological potential of these natural products. According to PASS (Prediction of Activity Spectra for Substances) estimates, they are more likely to exhibit antiprotozoal and antitumor properties. Some of them are now widely used in clinical medicine. All polycyclic endoperoxides presented in this article demonstrate antiprotozoal activity and can be divided into three groups. The third group includes endoperoxides, which show weak antiprotozoal activity with a reliability of up to 70%, and this group includes only 1.1% of metabolites. The second group includes the largest number of endoperoxides, which are 65% and show average antiprotozoal activity with a confidence level of 70 to 90%. Lastly, the third group includes endoperoxides, which are 33.9% and show strong antiprotozoal activity with a confidence level of 90 to 99.6%. Interestingly, artemisinin and its analogs show strong antiprotozoal activity with 79 to 99.6% confidence against obligate intracellular parasites which belong to the genera Plasmodium, Toxoplasma, Leishmania, and Coccidia. In addition to antiprotozoal activities, polycyclic endoperoxides show antitumor activity in the proportion: 4.6% show weak activity with a reliability of up to 70%, 65.6% show an average activity with a reliability of 70 to 90%, and 29.8% show strong activity with a reliability of 90 to 98.3%. It should also be noted that some polycyclic endoperoxides, in addition to antiprotozoal and antitumor properties, show other strong activities with a confidence level of 90 to 97%. These include antifungal activity against the genera Aspergillus, Candida, and Cryptococcus, as well as anti-inflammatory activity. This review provides insights on further utilization of polycyclic endoperoxides by medicinal chemists, pharmacologists, and the pharmaceutical industry.

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Computer-aided prediction of biological activity spectra for organic compounds: the possibilities and limitations

Cited by 65 publications

References 71 publications

Isoxazole derivatives of silatrane: synthesis, characterization, in silico ADME profile, prediction of potential pharmacological activity and evaluation of antimicrobial action

Isoxazole derivatives of silatrane: synthesis, characterization, in silico ADME profile, prediction of potential pharmacological activity and evaluation of antimicrobial action

Pharmacoinformatics and Preclinical Studies of NSC765690 and NSC765599, Potential STAT3/CDK2/4/6 Inhibitors with Antitumor Activities against NCI60 Human Tumor Cell Lines

Antiprotozoal and Antitumor Activity of Natural Polycyclic Endoperoxides: Origin, Structures and Biological Activity

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